Relatively little is known regarding the neuropsychological changes associated with multiple sclerosis (MS). It is our intent to define the cognitive and affective disturbance observed in patients with this demyelinating disease. Two groups of patients, MS (N=156) and neurological controls (N=60), will be randomly selected from a large representative patient pool and matched on the basis of age, education, occupation, sex and race. All subjects will be administered a battery of cognitive and affective psychometric tests, and will undergo a neurological examination (including measures of disability), magnetic resonance (MR) imaging, an examination of activities of daily living (ADL), and an assessment of educational/vocational activities. Sixty MS patients and all control patients will be re-evaluated after a three year interval. The objectives of this project are: (1) to determine the prevalence, type and severity of cognitive and effective disturbance in a large representative sample of patients with MS, (2) to examine the natural history of cognitive and affective disturbance in MS over a three year retest interval, (3) to identify the behavioral correlates of cerebral plaques and ventricular dilatation, as identified by MR imaging, (4) to assess the effects of cognitive and affective disturbance on ADL and educational/vocational activities, (5) to develop and validate a brief screening instrument to identify MS patients with cognitive disturbance, and (6) to study the relationship between cognitive and affective disturbance in MS.